AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation

J Exp Med. 2020 Jan 6;217(1):e20182009. doi: 10.1084/jem.20182009.


Activation of T cells is dependent on the organized and timely opening and closing of chromatin. Herein, we identify AP-1 as the transcription factor that directs most of this remodeling. Chromatin accessibility profiling showed quick opening of closed chromatin in naive T cells within 5 h of activation. These newly opened regions were strongly enriched for the AP-1 motif, and indeed, ChIP-seq demonstrated AP-1 binding at >70% of them. Broad inhibition of AP-1 activity prevented chromatin opening at AP-1 sites and reduced the expression of nearby genes. Similarly, induction of anergy in the absence of co-stimulation during activation was associated with reduced induction of AP-1 and a failure of proper chromatin remodeling. The translational relevance of these findings was highlighted by the substantial overlap of AP-1-dependent elements with risk loci for multiple immune diseases, including multiple sclerosis, inflammatory bowel disease, and allergic disease. Our findings define AP-1 as the key link between T cell activation and chromatin remodeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / immunology
  • Cells, Cultured
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly / immunology
  • Gene Expression Regulation / immunology
  • Humans
  • Hypersensitivity / immunology
  • Inflammatory Bowel Diseases / immunology
  • Lymphocyte Activation / immunology*
  • Multiple Sclerosis / immunology
  • T-Lymphocytes / immunology*
  • Transcription Factor AP-1 / immunology*


  • Chromatin
  • Transcription Factor AP-1